Regulation of the NLRP3 inflammasome by autophagy and mitophagy.

The NLRP3 inflammasome is a multiprotein complex that upon activation by the innate immune system drives a broad inflammatory response. The primary initial mediators of this response are pro-IL-1β and pro-IL-18, both of which are in an inactive form. Formation and activation of the NLRP3 inflammasome activates caspase-1, which cleaves pro-IL-1β and pro-IL-18 and triggers the formation of gasdermin D pores.

Gasdermin D and Gasdermin E Are Dispensable for Silica-Mediated IL-1β Secretion from Mouse Macrophages.

Silica crystals activate the NLRP3 inflammasome in macrophages, resulting in the caspase-1-dependent secretion of the proinflammatory cytokine IL-1β. Caspase-1-mediated cleavage of gasdermin D (GSDMD) triggers the formation of GSDMD pores, which drive pyroptotic cell death and facilitate the rapid release of IL-1β. However, the role of GSDMD in silica-induced lung injury is unclear.

Antibiotic use during influenza infection augments lung eosinophils that impair immunity against secondary bacterial pneumonia.

A leading cause of mortality after influenza infection is the development of a secondary bacterial pneumonia. In the absence of a bacterial superinfection, prescribing antibacterial therapies is not indicated but has become a common clinical practice for those presenting with a respiratory viral illness. In a murine model, we found that antibiotic use during influenza infection impaired the lung innate immunologic defenses toward a secondary challenge with methicillin-resistant Staphylococcus aureus (MRSA).

Inflammasome-Independent Roles of NLR and ALR Family Members.

Pattern recognition receptors, including members of the NLR and ALR families, are essential for recognition of both pathogen- and host-derived danger signals. Several members of these families, including NLRP1, NLRP3, NLRC4, and AIM2, are capable of forming multiprotein complexes, called inflammasomes, that result in the activation of pro-inflammatory caspase-1. However, in addition to the formation of inflammasomes, a number of these family members exert inflammasome-independent functions.

NLRP12-expressing dendritic cells mediate both dissemination of infection and adaptive immune responses in visceral leishmaniasis.

The NLR protein NLRP12 contributes to innate immunity, but the mechanism remains elusive. Infection of or wild-type mice with led to aberrant parasite tropism. Parasites replicated to higher levels in livers of mice than in the livers of WT mice and failed to disseminate to spleens.